In natural infections, human viruses normally encounter noncycling, terminally differentiated epithelial cells (J. Tooze, 1981, DNA Tumor Viruses, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.). To maximize the number of cells able to replicate the viral genome and the time spent in viral replication, it is thought that several RNA and DNA tumor viruses alter cell cycle controls (Braithwaite, A. W. et al., J. Virol. 45: 192-199 (1983)). Various serotypes of human adenoviruses, for example, induce cellular DNA synthesis by overcoming restriction point controls in the G1 phase of the cell cycle (Shimojo, H. and Yamashita, T., Virology 36: 422-433 (1968); Strohl, W. A., Virology 39: 653-665 (1969); Younghusband, H. B. et al., J. Gen Virol. 45, 455-468 (1979)). This phenomenon has also been observed for other tumor viruses, including simian virus 40 (Gershey, E. L. J. Virol. 30: 76-83 (1979)) and Rous sarcoma virus (Kobayashi, N. and A. Kaji, Proc. Natl. Acad. Sci. U.S.A. 75: 5501-5505 (1978)).
Adenoviruses also cause alterations in cell cycle progression in growing cells. The G1 phase is shortened in some cells, and DNA replication is uncoupled from the synthesis of rRNA and polyamines. Adenovirus-infected rodent cells prematurely initiate successive rounds of cellular DNA replication and become polyploid (Braithwaite, A. W. et al., J. Virol. 45: 192-199 (1983)).
Infection of stationary cells by DNA tumor viruses such as simian virus 40 leads also to the several-fold activation of enzymes in the deoxyribonucleic acid synthetic pathways (Hartwell, L. H. et al., Virology 27: 262-272 (1965)). Activation of some of these cellular enzymes in G1-arrested cells may play an important role in viral growth in arrested cells. Such alterations of the physiology of normal cells by the transforming proteins of DNA viruses and other viral proteins might allow more efficient viral replication and production of virus particles.